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M\u00f8ller og Hustru Chastine Mc-Kinney M\u00f8llers Fond til almene Formaal","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005747","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006356","name":"Syddansk Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006356","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004196","name":"Odense Universitetshospital","doi-asserted-by":"publisher","award":["A2998"],"award-info":[{"award-number":["A2998"]}],"id":[{"id":"10.13039\/501100004196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Superoxide anions can reduce the bioavailability and actions of endothelium\u2010derived NO. In human resistance\u2010sized arteries, endothelium\u2010dependent vasodilatation can be mediated by H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> instead of NO. Here, we tested the hypothesis that in resistance arteries from patients with cardiovascular disease, endothelium\u2010dependent vasodilatation is mediated by a reactive oxygen species and not impaired by oxidative stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Small arteries were isolated from biopsies of the parietal pericardium of patients undergoing elective cardiothoracic surgery and were studied using immunohistochemical and organ chamber techniques.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>NO synthases 1, 2 and 3, superoxide dismutase 1 and catalase proteins were observed in the microvascular wall. Relaxing responses to bradykinin were endothelium dependent. During submaximal depolarization\u2010induced contraction, bradykinin\u2010mediated relaxations were inhibited by inhibitors of NO synthases (NOS) and soluble guanylyl cyclase (sGC) but not by scavengers of NO or HNO, inhibitors of cyclooxygenases, neuronal NO synthase, superoxide dismutase or catalase, or by exogenous catalase. During contraction stimulated by endothelin\u20101, these relaxations were not reduced by any of these interventions except DETCA, which caused a small reduction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>In resistance arteries from patients with cardiovascular disease, endothelium\u2010dependent relaxations seem not to be mediated by NO, HNO or H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, although NOS and sGC can be involved. These vasodilator responses continue during excessive oxidative stress.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15712","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T20:39:57Z","timestamp":1634762397000},"page":"1049-1064","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nitric oxide (NO) synthase but not NO, HNO or H<sub>2<\/sub>O<sub>2<\/sub> mediates endothelium\u2010dependent relaxation of resistance arteries from patients with cardiovascular disease"],"prefix":"10.1111","volume":"179","author":[{"given":"Maximilian","family":"Matthies","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine University of Southern Denmark  Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristoffer","family":"Rosenstand","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Southern Denmark  Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inger","family":"Nissen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Southern Denmark  Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stan","family":"Muitjens","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Southern Denmark  Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars P.","family":"Riber","sequence":"additional","affiliation":[{"name":"Department of Cardiac, Thoracic and Vascular Surgery Odense University Hospital  Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6274-8071","authenticated-orcid":false,"given":"Jo G. 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